PROJECT SUMMARY Over the past decade, the U.S. Preventive Services Task Force, specialty organizations and the Advisory Committee on Immunization Practices have made significant changes to their guidelines on cancer screening, cardiovascular disease prevention and immunizations. In practice, there have been varied responses to these revisions with some guidelines being widely and rapidly adopted, and others being largely ignored. There is robust literature that seeks to understand the patient, clinician, practice and health system features that influence the adoption of new recommendations for individual services; yet, we lack an understanding of the complex interactions between, and the relative importance of, these four levels of influence across different guideline topics. In September 2013, our team began a large National Cancer Institute (NCI) funded dissemination trial involving 249,574 patients at 56 practices in eight states. The trial examines how a diverse cohort of practices field an application called an Interactive Preventive Health Record (IPHR), which is designed to promote evidence-based preventive and chronic care recommendations. The original development and testing of the IPHR was supported by the Agency for Healthcare Research and Quality. The current NCI dissemination trial seeks to understand the IPHR's influence on service delivery and shared decision-making. Three practice networks are collecting extensive data about participating health systems, practices, clinicians and patients, including data linked to the electronic health record. We have a unique opportunity, not within the scope of the current NCI dissemination trial, to evaluate a comprehensive set of factors that could influence the adoption of guideline changes covering a variety of conditions. We propose a mixed methods approach to studying the health system, practice, clinician and patient factors that influence the implementation of new guidelines. Data from the current NCI dissemination trial will be used to estimate the rates and timing of the implementation of guideline changes for breast, cervical, prostate and lung cancer screening; blood pressure and lipid management; and influenza and pneumococcal vaccinations. Specifically, adherence before and after guideline changes will be estimated and compared using a longitudinal four-level model for each preventive services, accounting for characteristics and variability at the patient, clinician, practice and health system levels. Specific variables for each of these levels are guided by using a novel framework based on existing evidence. The same hierarchical models will be used to explore characteristics at each level that are associated with guideline implementation, as well as with changes in guideline adherence over time. To better characterize these interacting variables, we will conduct semi- structured interviews with clinicians at practices that have either high or low implementation rates, as defined by a composite measure of guideline changes. This qualitative exploratory phase of our study will help inform future interventions to better disseminate and promote the implementation of future guideline changes.